Adaptive calibration for pulse oximetry

ABSTRACT

A method for calibrating a pulse oximeter device and an apparatus incorporating the method and a system for utilizing the method. The method is based on modeling light propagation in tissue at two wavelengths, typically, one in the red and one in the infrared range of the spectrum. A formula is derived relating the arterial oxygen saturation to a ratio R commonly measured by standard pulse oximeters. A specific parameter is identified and utilized in the calibration of the oximeter. This parameter is formulated in terms of the DC signals measured by the pulse oximeter at the two wavelengths. An empirical method for estimating this parameter based on experimental data is also described.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates generally to optical measurementdevices, and, more particularly, to pulse oximetry systems with a novelmethod of dynamically calibrating a pulse oximeter based upon empiricalinputs and a related parameter that is a function of the DC componentcommonly measured in pulse oximetry.

[0003] 2. Description of the Related Art

[0004] Oximetry is based on the principle that the color of blood isrelated to the oxygen saturation level of hemoglobin. For example, asblood deoxygenates, skin loses its pinkish appearance and takes on moreof a bluish tint. This principle permits measurement of the degree ofoxygen saturation of blood using what is commonly known as optical pulseoximetry technology.

[0005] Optical oximeters take advantage of the fact that oxygenated anddeoxygenated hemoglobin absorb visible and near infrared lightdifferently. Generally, blood perfused tissue is illuminated and lightabsorption by the tissue is determined by a suitable light sensor. Thelight absorption is then correlated with an estimated oxygen saturationlevel (SaO₂). In commonly used methods of pulse oximetry, the bloodperfused tissue is illuminated by light selected to have at least twodifferent wavelengths, preferably one in the red band and one in theinfrared band.

[0006] A distinct absorption corresponds to each wavelength of light,such that a specific absorption corresponds to each hemoglobin oxygensaturation value in the range 0-100%. See e.g., Physio-opticalconsiderations in the design of fetal pulse oximetry sensors, Mannheimeret al., European Journal of Obstetrics & Gynecology and ReproductiveBiology, 72 Suppl. 1 (1997). Accurate oximeter performance requires agood overlap of light penetration in tissue at the chosen wavelengths soas to minimize the effects of tissue heterogenicity.

[0007] Pulse oximeter oxygen saturation level readings are denoted bySpO₂, whereas oxygen saturation in arterial blood samples based ondirect in vitro measurement are denoted SaO₂. The pulse oximetry oxygensaturation level (SpO₂) is determined by positioning the blood-perfusedtissue adjacent to a light source and a detector, passing a light ofeach of two wavelengths through the tissue, measuring the constant andpulsatile light intensities at each wavelength, and correlating them toan SpO₂ reading.

[0008] Values of light absorption measured in pulse oximetry generallyinclude a constant (non-pulsatile) component and a variable (pulsatile)component. The constant component is commonly referred to as the “DC”component. The measured DC component is influenced by several factors,such as the light absorbency of the biological tissue, the presence ofvenous blood, capillary blood, and non-pulsatile arterial blood, thescattering properties of tissue, the intensity of the light source, andthe sensitivity of the detector.

[0009] The variable component results from the pulsatile flow ofarterial blood through the tissue being probed. This pulsatile flow,corresponding to the systole phase of the cardiac cycle, acts such thatlight absorption varies proportionately to the flow of blood. Thisvariable absorption of light through tissue (the pulsatile component) iscommonly referred to as the “AC” component. Because pulsing is afunction of the fluctuating volume of arterial blood, the AC lightintensity level fairly represents the light absorption of the oxygenatedand deoxygenated hemoglobin of arterial blood.

[0010] To determine a ratio (R) of pulsatile light intensities tonon-pulsatile light intensities, the constant DC component of the lightintensity must be factored out. The amplitudes of both the AC and DCcomponents are dependent on the incident light intensity. Dividing theAC level by the DC level gives a “corrected” AC level that is no longera function of the incident light intensity. Thus, ratioR=(AC1/DC1)/(AC2/DC2) is an indicator of arterial SaO₂. Conventionally,an empirically derived calibration curve for the relationship betweenthe above ratio R and SaO₂ provides the pulse oximetry oxygen saturationlevel SpO₂.

[0011] In oximetry, the measured transmission of light traveling throughblood-perfused tissue, and the pulse oximetry oxygen saturation level(SpO₂), are therefore based upon two things: one, the natural differencein light absorption in oxygenated hemoglobin and deoxygenatedhemoglobin; and two, the detected change in light absorption resultingfrom the fluctuating volume of arterial blood passing through the tissuebetween the light source and the sensor, i.e., the pulsatile component.The amplitude of the pulsatile component is a small fraction of thetotal signal amplitude, so small changes in the pulsatile component maybe “lost” in the background of the total signal amplitude.

[0012] By relying on the pulsatile component in this manner, currentpulse oximeters and methodologies cannot effectively account for lightscattering and absorption of light in the biological tissues that arebeing probed. Thus, current techniques use empirical data and factor inan average component for scattering and absorption. See e.g., PulseOximetry: Theoretical and Experimental Models. De Kock, et al., Medicaland Biological Engineering & Computing, Vol. 31, (1993). This approachresults in oximeters that rely upon fixed calibration curves to predictSpO₂ from measured electronic signals.

[0013] The current practice in pulse oximetry of subsuming thescattering and absorption of light that occurs in tissue by resorting toempirical calibration techniques is problematic. While it may beacceptable at oxygen saturation levels within normal ranges for adults,i.e., 70% to 100% SaO₂, it becomes less acceptable when oxygensaturation is in the lower range, for example, of 15% to 65% SaO₂. Thislower range represents severe hypoxia in post-natal subjects, and isalso commonly encountered in fetal oximetry. Both of these circumstancesrequire accurate and reliable oxygen saturation estimates.

[0014] In oximeters with larger probes, e.g., probes having a pathlengthbetween the emitter and detector that would encompass a finger, foot orearlobe, the conventional approach to calibration is acceptable becausescatter and absorption are less of an issue. As the probe sizedecreases, however, and the pathlength becomes shorter, e.g., fetaloximeter probes, the error due to background scattering and absorptionhas a relatively greater impact on oximeter accuracy.

[0015] Precise estimation of SpO₂ with probes having a pathlength lessthan 5 mm is difficult due to the scattering and absorption of light intissue. The challenge, therefore, is to account for scattering andabsorption through their relationship to the measured DC and AC signals.

[0016] Approaches have been described in the literature wherein thescattering and absorption characteristics of the tissue being probed aretheoretically modeled. See e.g., Diffusion-based model of pulseoximetry: in vitro and in vivo comparisons, Marble et al., AppliedOptics, Vol.33, No. 7 (1994); Pulse Oximetry: Theoretical andExperimental Models, Kock et al., Med. & Biol. Eng. & Comput., Vol. 31(1993). One problem with the theoretical approach is that the totalnumber of variables used in the various models make it difficult toaccurately model these characteristics. This results in furtherapproximations, and in an inevitable “guessing” of some of theparameters. For example, in order to calculate absorption from the DCsignal, one has to guess scattering. Similarly, where one wants tocalculate scattering from the DC signal, absorption has to beapproximated.

[0017] Furthermore, inter-patient and intra-patient variation betweenthe biological tissues that are probed, present a significant challengeto the purely theoretical approach. This variation precludes themodeling of scattering and absorption in a dynamic fashion. Neither thecurrently employed empirical approach, nor the theoretical modelscurrently described, are as accurate or dynamic as the calibrationtechniques of the present invention.

[0018] The present invention differs from conventional techniques inthat it does not use an arbitrary guess for scattering, but instead usesclinical data to evaluate an average scattering, and incorporates thatvalue into a parameter identified as k_(DC). In particular, thefunctional dependence of k_(DC) on the measured signals AC and DCdepends on the average scattering which is derived from the clinicalstudies.

SUMMARY OF THE INVENTION

[0019] In pulse oximetry, the intensity of light, T, transmitted throughtissue is measured. The arterial oxygen saturation, SaO₂, is calculatedfrom the changes introduced in T due to the time-varying volume, i.e.,pulsing, of arterial blood and the different absorption properties ofoxygenated and deoxygenated hemoglobin. Changes in arterial blood volumeintroduce corresponding changes to hemoglobin absorption, and hence,changes to the total absorption coefficient of light in tissue, μ_(a).In turn, these changes affect the light transmission measured signal T.

[0020] Determining oxygen saturation by pulse oximetry generallyinvolves two steps. First, changes in the hemoglobin absorption oftissue due to the pulsatile flow of blood must be evaluated. The changesin hemoglobin absorption are dependent upon SaO₂. Second, the changes inthe measured signal, T, must be related to the absorption changes suchthat: T→μ_(a)→SaO₂.

[0021] In pulse oximetry, relating the changes in the measured signal Tto the change in absorption μ_(a) poses problems. In essence, thechallenge is in the nature of a radiative transport problem, namely, howto account for the absorption and scattering of light in biologicaltissue.

[0022] Accordingly, the present invention is an improved hybridcalibration methodology preferably based on a combination of theoreticaland empirical inputs that account for the scattering and absorption oflight in tissue. The calibration methods can be utilized in a dynamicmanner so as to adaptively calibrate the oximeter based on changinginputs, thereby improving the accuracy and precision of the oxygensaturation predictions. The methodology is applicable over a wide rangeof oxygen saturation levels and a variety of probe configurations andsizes, but is particularly applicable to circumstances where loweroxygen saturation levels are typically encountered, and/or with probeshaving a relatively short pathlength between the emitter and detector.

[0023] Additionally, a method and apparatus for conducting pulseoximetry are provided that account for the scattering and absorption oflight in biological tissue.

[0024] It is an object of the present invention to provide an improvedcalibration methodology that need not rely on fixed calibration curves.In particular, the present invention provides a method of calibrating apulse oximeter wherein the light propagation in tissue is preferablymodeled for two distinct wavelengths such that the effects of thescattering and absorption of light in the tissue are incorporated intothe resulting oxygen saturation prediction. According to one aspect ofthe invention, the scattering and absorption of light in tissue arepreferably formulated into a determinable parameter based on commonlymeasured values.

[0025] In a presently preferred embodiment, experimental data isgathered and assimilated such that a new parameter, k_(DC), isdetermined to be a function of the typical measured DC value. In thismanner, parameter k_(DC) is calculated utilizing subsequently detectedDC signals, and, therefore, a reference is made to previously obtainedexperimental data to accurately predict SpO₂ based upon the detected DCsignal.

[0026] Also provided is a method of performing optical oximetry whereinlight is transmitted, detected and measured, and the resultingmeasurements are used to formulate a corresponding ratio R. The DCsignals are measured and used to calculate k_(DC) and then k_(DC) and Rare multiplied together and are used together and the resulting value isused to determine an SpO₂ value.

[0027] In another embodiment, a processing system is provided to controlthe emission of light, the detection of light, the calibration of thedetected signals based on the methods described herein, and to calculateand predict SaO₂.

[0028] In a presently preferred embodiment, the calculating stepincorporates the measured DC value. In other embodiments, thecalculating step also incorporates the partial derivative D_(r) in thecalculation of k_(DC) The calculating step incorporates changes in thescattering and absorption of light in tissue as a function of themeasured signals, thereby allowing for an adaptive method of calibratingan oximeter.

[0029] These and other objects, features and characteristics of thepresent invention, as well as the methods of operation and functions ofthe related elements of structure and the combination of parts andeconomies of manufacture, will become more apparent upon considerationof the following description and the appended claims with reference tothe accompanying drawings, all of which form a part of thisspecification, wherein like reference numerals designate correspondingparts in the various figures. It is to be expressly understood, however,that the drawings are for the purpose of illustration and descriptiononly and are not intended as a definition of the limits of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0030]FIG. 1 is a diagram showing one arrangement of components suitablefor use to practice oximetry technique and the method of calibrating anoximeter in accordance with the principles of the present invention;

[0031]FIG. 2A is an example of a reflectance-type probe;

[0032]FIG. 2B is a depiction of a non-invasive oximetry technique;

[0033]FIG. 3A is an example of a transmission-type probe commonly usedin conducting fetal oximetry;

[0034]FIG. 3B is an enlargement of the sensor of FIG. 3A showing aspiral needle and depicting the location of a light source and detectorfor an invasive oximetry probe;

[0035]FIG. 4A is a generalized flow diagram of the process of thepresent invention;

[0036]FIG. 4B is a detailed schematic flow diagram showing bothProspective and Retrospective sequences of (i) obtaining calibrationdata, and (ii) using the oximeter with the calibration data inaccordance with the present invention;

[0037]FIG. 5A shows the calibration curve SpO₂ vs. R obtained byemploying a prior art method to obtain a fixed calibration curve fordata from three clinical cases;

[0038]FIG. 5B shows the correlation between SaO₂, as measured by a bloodgas analyzer, and SpO₂, as measured by an oximeter using the prior artpractice of employing a fixed calibration curve;

[0039]FIG. 6A shows the calibration curves for SpO₂ vs. R obtained byaccounting for the scattering and absorption of light by employingEquation (17) for the same data from three clinical cases depicted inFIG. 5A;

[0040]FIG. 6B shows the correlation between SaO₂, as measured by a bloodgas analyzer, and SpO₂, as measured by an oximeter employing the dynamiccalibration methodology of the present invention as represented byEquation (17);

[0041]FIG. 7A shows the calibration curves for SpO₂ vs. R obtained byemploying Equation (21) for the same data from three clinical casesdepicted in FIGS. 5A and 6A;

[0042]FIG. 7B shows the correlation between SaO₂, as measured by a bloodgas analyzer, and SpO₂, as measured by an oximeter employing the dynamiccalibration methodology of the present invention by incorporating theparameter D_(r) as shown in Equation (21);

[0043]FIG. 8 shows the linear relationship between k_(DC) and R for theclinical data and which can be represented by Equation (22); and

[0044]FIG. 9 shows the relationship between D_(r) and Ratio$\xi = \frac{D\quad {C({red})}}{D\quad {C({ir})}}$

[0045] and

[0046] which is shown in Equation (20) and used in Equation (21).

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS OF THEINVENTION

[0047] The oximetry measurement devices, calibration systems andmethodologies of the present invention are applicable to most, if notall, current oximetry devices and practices. For example, FIG. 1 depictsa block diagram showing the general arrangement of an oximetry systemthat includes a control unit 10, a light source 20, a light detector 30,a measuring unit 40, and a processing unit 50. Control unit 10 iscoupled to light source 20 to activate the transmission of light. Topractice the present invention, tissue 60 is positioned between (fortransmission oximetry) or against (for reflectance oximetry) lightsource 20 and light detector 30. In this arrangement, light source 20outputs light of one or more wavelengths, and preferably two or morewavelengths, wherein at least one wavelength is in the red range and onein the infrared (ir) range.

[0048] Processing unit 50 is coupled to control unit 10 to coordinatethe transmitted light and detected light. Light source 20 produces lighthaving the desired wavelength(s) which is then transmitted through thetissue 60 to light detector 30 along optical measurement path 25. Lightdetector 30 is coupled to measuring unit 40, which measures the lightintensity incident on light detector 30. Measuring unit 40 is coupled toprocessor unit 50, which receives and processes the light intensitymeasurement to produce measurement 70. Measurement 70 is typically theresult of processing light intensity measurement T into the output SpO₂.

[0049] In accordance with the present invention, the process oftransmitting and detecting light through tissue can be undertaken in avariety of ways. For example, FIG. 2A shows a reflectance probe 90wherein a light source 100 is placed near the tissue to be probed, andlight is emitted into the tissue. Light is reflected back out of thetissue and is detected by detector 110, 30, which sends a signal viacable 120 and connector 130 to a pulse oximeter processor and monitor(not shown) and processed.

[0050] As schematically shown in FIG. 2B, it is well known to usemultiple wavelengths of light in reflectance (as well as transmission)oximetry. Typically a red 170 and an ir 180 wavelength are chosenwhereby the differing wavelengths of light pass through discrete layersof the tissue, e.g., skin 190, fat 192, muscle 194 and bone 196, beingprobed.

[0051]FIG. 3A shows an example of an invasive probe 200 that is commonlyused in conducting fetal oximetry. A light source and detector on asensor 250 is imbedded subcutaneously into the fetal tissue. FIG. 3Ashows the sensor housed in a sheath 210 prior to being placed in apatient. FIG. 3B shows an enlargement of probe/sensor 250. In thisspiral needle probe 250, a light emitter 220 and a light detector 230are in very close proximity, such as less than one centimeter apart.Other types of transmission-probe arrangements that are non-invasiveand/or allow the transmission of light through an ear lobe or finger,typically will have a greater distance, and hence a longer pathlength,between the light source and light detector.

[0052] The specific aspects of the present invention are describedwithout reference to any one particular type of probe, because thecalibration techniques of the present invention are applicable to alltypes of oximetry devices. Thus, the calibration techniques of thepresent invention are suitable for use with reflectance-type probes,like those shown in FIG. 2A, and transmissive-type probes, like thoseshown in FIGS. 3A and 3B, as well as any other invasive or non-invasiveprobes. In addition to these probe types, the systems and methodologiesof the invention are applicable to virtually any type of oximetry probeconfiguration.

[0053] To practice the invention with any type of measuring device orsystem, e.g., transmission, reflectance, invasive, non-invasive, what isneeded is to determine the relationship between the probe geometry andmeasured signal T, and then to develop appropriate calibration curves orequations through clinical trials. This process is shown generally inFIG. 4A and is discussed in greater detail with reference to FIG. 4B.

[0054] I. Basic Oximetry Calibration Equations

[0055] Pulse oximetry generally utilizes two wavelengths of light, onein the red wavelength (red) range (typically 630-760 nm) and one in theinfrared wavelength (ir) range (typically 880-960 nm). The absorptioncoefficients of oxygenated hemoglobin and deoxygenated hemoglobin at redcan be represented as μ_(OX) (red) and μ_(DX) (red), respectively.Similarly, the corresponding absorption coefficients at infrared (ir)can be represented as μ_(OX) (ir) and μ_(DX) (ir).

[0056] By designating the total concentrations of oxygenated anddeoxygenated hemoglobin as c_(OX) and c_(DX) respectively, the totalhemoglobin absorption of light for each of the red and ir wavelengths,μ_(a), can be given by Equations (1) and (2) such that: $\begin{matrix}{{\mu_{a}({red})} = {{c_{OX}{\mu_{OX}({red})}} + {c_{DX}{\mu_{DX}({red})}}}} & \left( {{Equation}\quad 1} \right) \\{{\mu_{a}({ir})} = {{c_{OX}{\mu_{OX}({ir})}} + {c_{DX}{\mu_{DX}({ir})}}}} & \left( {{Equation}\quad 2} \right)\end{matrix}$

[0057] Equations (1) and (2) can then be solved to obtain the totaloxygenated (c_(OX)) and deoxygenated (c_(DX)) hemoglobin concentrationssuch that: $\begin{matrix}{c_{OX} = \frac{{{\mu_{a}({red})}{\mu_{DX}({ir})}} - {{\mu_{a}({ir})}{\mu_{DX}({red})}}}{{{\mu_{OX}({red})}{\mu_{DX}({ir})}} - {{\mu_{OX}({ir})}{\mu_{DX}({red})}}}} & \left( {{Equation}\quad 3} \right) \\{c_{DX} = \frac{{{\mu_{a}({ir})}{\mu_{OX}({red})}} - {{\mu_{a}({red})}{\mu_{OX}({ir})}}}{{{\mu_{OX}({red})}{\mu_{DX}({ir})}} - {{\mu_{OX}({ir})}{\mu_{DX}({red})}}}} & \left( {{Equation}\quad 4} \right)\end{matrix}$

[0058] As noted above, arterial pulses (corresponding to the systolicportion of the cardiac cycle) cause an increase in the volume ofarterial blood in the tissue being probed, i.e., a pulsatile change.This increase in arterial blood introduces a corresponding change in theoxygenated and deoxygenated hemoglobin concentrations. These changes canbe denoted c′_(OX) and c′_(DX) respectively. As a consequence of thepulsatile change in arterial blood volume, the total hemoglobinabsorption of light, μ_(a), also changes for each of the red and irwavelengths, and can be given by Equations (5) and (6) such that:$\begin{matrix}{{\mu_{a}^{\prime}({red})} = {{c_{OX}^{\prime}{\mu_{OX}({red})}} + {c_{DX}^{\prime}{\mu_{DX}({red})}}}} & \left( {{Equation}\quad 5} \right) \\{{\mu_{a}^{\prime}({ir})} = {{c_{OX}^{\prime}{\mu_{OX}({ir})}} + {c_{DX}^{\prime}{\mu_{DX}({ir})}}}} & \left( {{Equation}\quad 6} \right)\end{matrix}$

[0059] Equations (5) and (6) can then be solved to obtain the totalchange in the oxygenated and deoxygenated hemoglobin concentrationsattributable to arterial pulsing (c′_(OX) and c′_(DX)) such that:$\begin{matrix}{c_{OX}^{\prime} = \frac{{{\mu_{a}^{\prime}({red})}{\mu_{DX}({ir})}} - {{\mu_{a}^{\prime}({ir})}{\mu_{DX}({red})}}}{{{\mu_{OX}({red})}{\mu_{DX}({ir})}} - {{\mu_{OX}({ir})}{\mu_{DX}({red})}}}} & \left( {{Equation}\quad 7} \right) \\{c_{DX}^{\prime} = {\frac{{{\mu_{a}^{\prime}({ir})}{\mu_{OX}({red})}} - {{\mu_{a}^{\prime}({red})}{\mu_{OX}({ir})}}}{{{\mu_{OX}({red})}{\mu_{DX}({ir})}} - {{\mu_{OX}({ir})}{\mu_{DX}({red})}}}.}} & \left( {{Equation}\quad 8} \right)\end{matrix}$

[0060] The saturation of arterial hemoglobin, SpO₂, is then given byEquation (9) as follows: $\begin{matrix}{{SpO}_{2} = {\frac{c_{OX}^{\prime} - c_{OX}}{\left( {c_{OX}^{\prime} - c_{OX}} \right) + \left( {c_{DX}^{\prime} - c_{DX}} \right)} = \frac{1}{1 - \frac{{{x\mu}_{OX}({ir})} - {\mu_{OX}({red})}}{{{x\mu}_{DX}({ir})} - {\mu_{DX}({red})}}}}} & \left( {{Equation}\quad 9} \right)\end{matrix}$

[0061] In Equation (9), parameter x is defined by Equation (10) suchthat: $\begin{matrix}{x = {\frac{{\mu_{a}^{\prime}({red})} - {\mu_{a}({red})}}{{\mu_{a}^{\prime}({ir})} - {\mu_{a}({ir})}} = {\frac{\Delta \quad {\mu_{a}({red})}}{\Delta \quad {\mu_{a}({ir})}}.}}} & \left( {{Equation}\quad 10} \right)\end{matrix}$

[0062] According to Equation (9), the arterial hemoglobin saturation isa function of x, which represents the fractional change in theabsorption coefficient μ_(a), at the two wavelengths of interest, onered and one ir.

[0063] II. Introduction of k_(DC)

[0064] Accurate oximetry depends upon being able to relate the changesin absorption to the measured signal T. A small change in the absorptioncoefficient, Δμ_(a), introduces a corresponding change, ΔT, to themeasured signal T. In general, the AC signal is proportional to ΔT, andthe DC signal is proportional to T as shown by Equation (11) such that:$\begin{matrix}{{\Delta \quad T} = {\left. {\frac{\partial\quad T}{\partial\quad \mu_{a}}\Delta \quad \mu_{a}}\Rightarrow{\Delta \quad \mu_{a}} \right. = \frac{({AC})}{\left. \frac{\partial\quad T}{\partial\quad \mu_{a}} \right|_{\mu_{a} = {\mu_{a}{({DC})}}}}}} & \left( {{Equation}\quad 11} \right)\end{matrix}$

[0065] Note that Equation (11) requires knowledge of the dependence ofthe measured signal T on the absorption μ_(a). In general, T is afunction of the scattering and absorption coefficients denoted μ′_(s)and μ_(a), respectively, such that: T=T(μ_(a), μ′_(s)).

[0066] The exact form of T(μ_(a), μ′_(s)) depends on the specific probegeometry employed for the delivery (transmission) and collection(detection) of the light. In general, T cannot be fully derivedtheoretically, because the equation it obeys (i.e., the radiativetransfer equation, plus the appropriate boundary conditions) cannot besolved theoretically. The dependence of T on scattering and absorptioncan, however, be determined experimentally for a given probe geometry.One way that this can be done, for example, is by using a series oftissue phantoms with known scattering and absorption properties. Anotherway is to conduct clinical trials with experimental subjects. Once T isdetermined experimentally, (either with tissue phantoms or experimentalsubjects) the expression can be inverted and rewritten as shown byEquation (12) such that:

μ_(a)=μ_(a)(T,μ′_(s))  (Equation 12)

[0067] and the derivative in Equation (11) can thus be evaluated.

[0068] Equation (12) can then be used to calculate the fractional changein the absorption x in terms of the AC and DC signals for thatparticular probe, i.e., signals typically measured by oximeters, suchthat: $\begin{matrix}{{x = {\frac{\Delta \quad {\mu_{a}({red})}}{{\Delta\mu}_{a}({ir})} = {\left. \frac{\left. \frac{\partial T}{\partial\mu_{a}} \middle| {}_{\mu_{a} = {\mu_{a}{({ir})}}}{A\quad {C({red})}} \right.}{\left. \frac{\partial T}{\partial\mu_{a}} \middle| {}_{\mu_{a} = {\mu_{a}{({red})}}}{A\quad {C({ir})}} \right.}\Rightarrow x \right. = {k_{DC}R}}}}{with}} & \left( {{Equation}\quad 13} \right) \\{{k_{DC} = \frac{\left. \frac{\partial T}{\partial\mu_{a}} \middle| {}_{\mu_{a} = {\mu_{a}{({ir})}}}{{DC}({red})} \right.}{\left. \frac{\partial T}{\partial\mu_{a}} \middle| {}_{\mu_{a} = {\mu_{a}{({red})}}}{{DC}({ir})} \right.}}{and}} & \left( {{Equation}\quad 14} \right)\end{matrix}$

$\begin{matrix}{R = \frac{\left. {({AC})/({DC})} \right|_{red}}{\left. {({AC})/({DC})} \right|_{ir}}} & \left( {{Equation}\quad 15} \right)\end{matrix}$

[0069] Thus, parameter k_(DC) is a function of the DC signal only, and Ris the AC/DC ratio as defined in pulse oximetry. As shown above,parameter k_(DC) incorporates the effects of scattering and absorption.Accordingly, for a given value of k_(DC), there is a correspondingcalibration curve SaO₂(R). Thus, the dependence of SaO₂ on R is fullydefined and fixed, once k_(DC) is fixed. (In that sense, a new k_(DC)value corresponds to a new SaO₂ vs. R curve).

[0070] In traditional pulse oximetry, scattering is ignored and theBeer-Lambert exponential attenuation of light in tissue is assumed tohold such that T=e^(−μ) ^(_(a)) ^(L), where L is the tissue thickness.Under this assumption, $\begin{matrix}{{\Delta\mu}_{a} = {{{- \frac{1}{L}}\Delta \quad \frac{T}{T}} = {\left. {{- \frac{1}{L}}\frac{({AC})}{({DC})}}\Rightarrow x \right. = {\frac{{\Delta\mu}_{a}({red})}{{\Delta\mu}_{a}({ir})} = {\frac{\left. {({AC})/({DC})} \right|_{red}}{\left. {({AC})/({DC})} \right|_{ir}} = R}}}}} & \left( {{Equation}\quad 16} \right)\end{matrix}$

[0071] Inserting the above result into Equation (13) confirms that thebasic approximation of traditional pulse oximetry is expressed byk_(DC)=1, i.e., the effects of background absorption and scattering areignored, when, however, it is known that k_(DC) is not always equal to1.

[0072] Determining k_(DC) using the approach outlined in Equation (14)provides for a better accounting of the absorption and scattering oflight in biological tissue compared to the traditional approach ofignoring the effects of background absorption and scattering. In thisway, the introduction of the k_(DC) parameter represents a significantimprovement in the calibration of a pulse oximeter by employing bothempirical and theoretical inputs into the prediction equation.

[0073] III. Use of k_(DC) to Determine Oxygen Saturation

[0074] The calibration techniques of the invention are applicable to alltypes of measuring devices. To practice the invention with any type ofmeasuring device, what is required, in general terms is to determine therelationship between the probe geometry, the measured signals, and todevelop the appropriate calibration curves for example, through clinicaltrials. FIG. 4A describes the general process of the present invention.For example, in step 400 the probe is calibrated using experimentalsubjects and by conducting clinical trials as described in detail belowin “Confirmation of k_(DC) Clinical Evaluation.” Alternately, tissuephantoms with known light scattering and light absorption properties maybe employed. The data obtained in step 400 is compiled into a databasein step 410.

[0075] Once the probe has been calibrated in step 400 and the datacompiled in step 410, the oximetry device is used on prospectivesubjects in step 420. By measuring the AC and DC signals (i.e. signalsnormally measured) during step 420, and comparing the measured signalsto the database 410, a value for k_(DC) can be determined.

[0076] One method of obtaining k_(DC) is by determining its functionaldependence on DC, as generally outlined in step 430. Another method ofobtaining k_(DC) is by determining its functional dependence onderivative D_(r), as generally outlined in step 440. Once k_(DC) isobtained by either pathway 430, 440 (or through other means), the valuefor k_(DC) is used to arrive at an SpO₂ value that accounts for thescattering and absorption of light 450 and accurately reflects thesubjects SaO₂ status.

[0077] Specifically, this process is undertaken, in an exemplaryembodiment of the present invention, as described in FIG. 4B. Forexample, on the “Retrospective” side of the flow chart, the processbegins by selecting 500 an oximeter device and a probe having a red andir source of light and a fixed path length between the light source anddetector. Through the use of an experimental subject 510, therelationship between the measured signals and the blood gas SaO₂ valueare determined by subjecting the probe to one or more clinical trialsand characterizing, and collecting the data 520.

[0078] Once the data has been collected, the relationship is developedand the probe is calibrated 530 from the clinical data by estimating thefunctional dependence of parameter k_(DC) on the measured DC ratio overa range of SaO₂ oxygen saturations. This calibration data is compiled540 into database of functional dependence of k_(DC) 660 on one or moremeasured variables, e.g., on R as depicted in FIG. 8, or as depicted inFIG. 9.

[0079] Once these retrospective steps have been undertaken, oximetryproceeds in typical fashion, for instance, as shown in FIG. 4B on the“Prospective” side of the flow chart. With reference to FIG. 4B, afterconnecting the pre-calibrated probe to an oximeter device 600, oximetrycan proceed as described below.

[0080] First, the probe is located such that the patient's tissue ofinterest 610 is between (for transmission oximetry) or adjacent to (forreflectance oximetry) the light source and light detector. Next, lightis transmitted through the patient's tissue 610 and the AC and DC valuesare measured 620 and the Ratio (R) of pulsatile light intensities tonon-pulsatile light intensities are calculated using Equation (15).

[0081] At this point, ratio R is used to arrive at a value for k_(DC) ina number of ways. One avenue is to go directly to the database offunctional dependence of k_(DC) 660 via step 640. FIG. 8 (discussedbelow) depicts an example of the functional dependence of k_(DC) on R.In proceeding along this path 640, the Equation (22), as shown anddiscussed below, is used to obtain k_(DC). After arriving at a value fork_(DC) in this manner, the k_(DC) value is inputted 670 into Equation(9) and an SpO₂ value is generated in step 680.

[0082] An alternate pathway to k_(DC) from step 620 is through step 615.In step 615 the measured DC signals are used to select derivativevariable D_(r) via the Ratio $\xi = \frac{{DC}({red})}{{DC}({ir})}$

[0083] Variable D_(r) is defined by Equation (18) which is discussed indetail and

[0084] shown below. In this manner, a table of expressions can beformulated over a range of ratios. With reference to FIG. 9, a graphicalexample of the data obtained in step 615 is shown. Following thederivation of D_(r) in step 615, k_(DC) can be determined by 650 entryinto the previously compiled database 660. The parameter k_(DC) can thenbe obtained using Equation (21). Via step 670, k_(DC) is input such thatSpO₂ can be output with Equation (9) in step 680.

[0085] IV. Confirmation of k_(DC) Via Clinical Evaluation

[0086] Typically, the ratio R is used to predict SpO₂ as shown in FIG.5A. An example of the correlation between predicted SpO₂ to measuredSaO₂ using previous oximetry practices, i.e., without incorporating theeffects of light scattering and absorption, is shown in FIG. 5B. Themethods and techniques of the present invention increase thepredictability of SaO₂, as shown in FIGS. 6B and 7B.

[0087] To evaluate the increased predictability of SaO₂ by incorporatingk_(DC) into the calibration process of SpO₂ measurement, a series of invivo trials were conducted. The trials utilized time-dated pregnant eweswith singleton fetuses. The ewes were housed indoors in individual studycages and acclimated to controlled conditions of light (0600-1800 hrs.)and temperature (72° F.). Water and food were provided ad libitum,except for a 24-hour period prior to surgery. Under general anesthesia,the ewes were prepared with vascular catheters (femoral artery and vein)and a tracheal catheter. Fetuses were prepared with carotid artery andjugular vein catheters and two fetal scalp oximetry electrodes securedto the fetal head. An amniotic fluid catheter was also inserted. Thestudy was performed in anesthetized ewes with fetuses maintained withinthe uterus.

[0088] The study consisted of a 1 hour basal period followed by a3.5-hour hypoxia. During the basal period a maternal tracheal infusionof compressed air (5 L/min.) was administered continuously. Fetal andmaternal heart rate and fetal oximetry were monitored continuously.Maternal arterial and fetal arterial and venous blood samples were drawnat 15 minute intervals for determination of pH, pO₂, pCO₂, SO₂, andHCO₃. At the end of the basal period, the maternal tracheal infusion waschanged to a mixture of air and nitrogen gas with the rate beingadjusted at 30 minute intervals to achieve a ramped 30 percentage pointdecrease, e.g., 50% to 20%, in fetal oximetry (SpO₂) in five (5)percentage point increments. The nitrogen mixture was titrated tomaintain each SO₂ value for 30 minutes. After a ramped 30 percentagepoint decrease, fetal SO₂ was ramped back up to the basal value.

[0089] Fetal scalp oximetry (SpO₂) was correlated with arterial andvenous SO₂. Using Equation (14), k_(DC) is estimated, in one embodimentof the present invention, i.e., by ignoring the effects of backgroundabsorption and scattering, as follows: $\begin{matrix}{k_{DC} \cong \frac{{DC}({red})}{{DC}({ir})}} & \left( {{Equation}\quad 17} \right)\end{matrix}$

[0090]FIG. 6A, illustrates calibration curves 100 a, 100 b, and 100 cobtained using Equation (17) for three clinical cases using aRespironics Fetal Oximeter of the type described in U.S. applicationSer. No. 09/581,122 on sheep fetuses. The contents of U.S. applicationSer. No. 09/581,122 are incorporated herein by reference. FIG. 6B showsthe correlation 102 between arterial hemoglobin oxygen saturationmeasured by the pulse oximeter (SpO₂) vs. the corresponding arterialsaturation (SaO₂) measured using a blood gas analyzer.

[0091] The approximation shown in Equation (17) in the evaluation ofk_(DC) is based on the assumption that background absorption andscattering are ignored, such that: $\begin{matrix}{D_{r} = {\frac{\left. \frac{\partial T}{\partial\mu_{a}} \right|_{\mu_{a} = {\mu_{a}{({ir})}}}}{\left. \frac{\partial T}{\partial\mu_{a}} \right|_{\mu_{a} = {\mu_{a}{({red})}}}} \cong 1}} & \left( {{Equation}\quad 18} \right)\end{matrix}$

[0092] Based on analysis of clinical data obtained from the experimentsdescribed above on sheep fetuses, it was determined, in actuality, that,

0.75<D _(r)<1.30  (Equation 19)

[0093] and, thus, Equation (17) constitutes an acceptable approximation.It should be noted that FIG. 6B illustrates the same data as FIG. 5B,however, the SpO₂ vs. SaO₂ graph has been drawn based upon k_(DC) beingcalculated with the estimation of Equation (17).

[0094] While there is no specific reason to choose a linearapproximation, a simple estimation of D_(r) is possible by assuming thatit is linearly dependent on the ratio of the DC signals such that$\xi = {\frac{{DC}({red})}{{DC}({ir})}.}$

[0095] By analyzing the clinical data obtained from the fetal sheep, thefollowing was derived: $\begin{matrix}{D_{r} = \left\{ \begin{matrix}{{{{- 10}\xi} + 6.6},{\xi < 0.59}} \\{{{{- 20}\xi} + 13.6},{0.59 \leq \xi < 0.62}} \\{{{{- 3.5}\xi} + 3.37},{0.62 \leq \xi < 0.74}} \\{{{{- 13.3}\xi} + 11.5},{0.74 \leq \xi < 0.78}} \\{{{{- 3.66}\xi} + 3.96},{\xi \geq 0.78}}\end{matrix} \right.} & \left( {{Equation}\quad 20} \right)\end{matrix}$

[0096] Where Equation (21) is used to calculate k_(DC) as follows:$\begin{matrix}{k_{DC} = {D_{r}{\frac{{DC}({red})}{{DC}({ir})}.}}} & \left( {{Equation}\quad 21} \right)\end{matrix}$

[0097] Alternate approximations that embody the k_(DC) parameter canalso be used in the practice of the present invention. For example,Equation (22) shows an alternative relationship between k_(DC) and R:

k _(DC) =aR+b.  (Equation 22)

[0098] In this equation, coefficients a and b are constants and havebeen determined from an analysis of the clinical data from the abovedescribed experiments to have optimal values of a=0.375, and b=0.225.

[0099] To practice the systems and methods of this invention byincluding k_(DC), (in correlating SaO₂ to SpO₂) the scattering andabsorption of light is accounted for, and the process and the predictionof SaO₂ is more precise. This holds true regardless of whether k_(DC) isobtained by way of derivative evaluation, e.g., Equation (21), orthrough linear expression, e.g., Equation (22).

[0100] For example, FIG. 7A shows the calibration curves needed topredict SaO₂ as a function of the parameter R based upon the same datafrom the sheep clinical trials shown in FIG. 6A. The difference betweenthe calibration curves of FIG. 7A and FIG. 6A is that in FIG. 7A, SaO₂is calculated using the derivative values shown in above Equation (21).

[0101]FIG. 5B shows SaO₂ as measured by a blood gas analyzer, comparedto SpO₂ as obtained by employing the traditional method of using a fixedcalibration curve, i.e., the current practice in the calibration ofpulse oximeters.

[0102]FIG. 6B shows SaO₂ vs. SpO₂ using estimation of D_(r)=1 asdetailed in Equation (18) above.

[0103]FIG. 7B incorporates the same data as in FIGS. 5B, i.e., fixedcalibration curve, and 6B, i.e., D_(r)≅1, but uses Equation (21) tofurther refine the correlation between SaO₂ by SpO₂.

[0104] Comparison of FIG. 5B with FIGS. 6B and 7B illustrates theimprovements in the SaO₂ prediction achieved by employing thecalibration techniques of the present invention.

[0105] While specific embodiments and methods for practicing thisinvention have been described in detail, those skilled in the art willrecognize various manifestations and details that could be developed inlight of the overall teachings herein. Accordingly, the particulararrangements disclosed are meant to be illustrative only and not tolimit the scope of the invention which is to be given the full breadthof the following claims and any and all embodiments thereof.

What is claimed is:
 1. A method of calibrating a pulse oximetercomprising: selecting a probe having an emitter, a detector, and apathlength between the emitter and detector; measuring transmission oflight through a tissue of interest with the probe; compiling a databaseof measured values characterizing the transmission of light through sucha tissue; formulating a value for a parameter k_(DC) as a function of atleast one of the measured values; and incorporating the parameter k_(DC)into a calibration equation for determining a value for SpO₂.
 2. Themethod of claim 1, wherein the tissue of interest is a living being. 3.The method of claim 2, wherein the steps of measuring, compiling,formulating, and incorporating are repeated for the living being over arange of SaO₂ levels.
 4. The method of claim 3, wherein the range ofSaO₂ levels is greater than 70%.
 5. The method of claim 3, wherein therange of SaO₂ levels is between about 15% and about 65%.
 6. The methodof claim 1, wherein the probe is an invasive probe.
 7. The method ofclaim 1, wherein the probe's pathlength is approximately 1 mm to about 5mm.
 8. The method of claim 1, wherein, in the formulating step, themeasured value includes a DC value.
 9. The method of claim 1, wherein,in the compiling step, the measured values includes an AC and a DCcomponent.
 10. The method of claim 1, wherein, before the incorporatingstep, the measured values are used to calculate a Ratio R.
 11. A methodof performing optical blood oximetry comprising: measuring thetransmission of light through tissue; determining at least one DC valuebased upon the transmission of light measurements; selecting acalibration parameter based upon the determined DC value; estimatingSaO₂ based upon the selected calibration parameter.
 12. The method ofclaim 11, further comprising the step of providing updated oxygensaturation estimates adapted to changes in the measured transmission.13. The method of claim 11, wherein the calibration parameter is k_(DC).14. The method of claim 13, wherein k_(DC) includes the partialderivation of values for D_(r).
 15. The method of claim 11, furthercomprising providing a pulse oximeter probe that includes a light sourcecapable of emitting light at two or more wavelengths, a detector, and ameasurable distance between the light source and the detector.
 16. Themethod of claim 11, wherein the step of determining further includes:quantifying an AC value based upon the transmission of light;calculating a Ratio R; and, relating R to the calibration parameter thataccounts for background absorption and scattering of light.
 17. Themethod of claim 16, wherein the relating step further includesdetermining a partial derivative D_(r) value, and using the D_(r) valueto relate R to the calibration parameter.
 18. The method of claim 16,wherein the calibration parameter is k_(DC).
 19. The method of claim 11,wherein the estimating step comprises: quantifying a k_(DC) value; andselecting a corresponding SaO₂ based upon previously determined clinicaldata.
 20. The method of claim 16, wherein the step of quantifyingincludes estimating a partial derivative D_(r) value.
 21. Aphysiological condition measuring device comprising: light generatingmeans; light detecting means, wherein an optical path having pathlengthis defined between the light generating means and the light detectingmeans; and a processing system that measures light incident upon thelight detecting means and returns a solution derived from previouslyobtained clinical data and being indicative of the physiologicalcondition based on the measured light.
 22. A measuring device accordingto claim 21, wherein the physiological condition is oxygen saturation.23. A measuring device of claim 21, wherein the processing systemproduces a measurement of SpO₂.
 24. A measuring device according toclaim 21, wherein the optical pathlength is less than about 1 cm.
 25. Ameasuring device according to claim 21, wherein the processing system iscalibrated to measure SaO₂ in a range of about 10% to about 70%.
 26. Anapparatus for determining oxygen saturation of hemoglobin in arterialblood using signals received from a probe, the signals being indicativeof the light absorption of arterial blood, which has pulsatile andnon-pulsatile components, at two or more light wavelengths, theapparatus comprising: means responsive to the signals received from theprobe; means for converting the signals received into data; memory meansfor storing the data; computing means for calculating parameters fromthe data; and means for relating the calculated parameters to apredicted arterial oxygen saturation.
 27. The apparatus of claim 22further comprising means for adaptively calibrating the predictedarterial oxygen saturation in response to the signals received from theprobe.
 28. The apparatus of claim 27, wherein the parameters calculatedby the computing means include a k_(DC) parameter
 29. A system forperforming pulse oximetry comprising: a probe including at least onelight source for transmitting light and at least one detector fordetecting the transmitted light; a processing system in communicationwith the probe so as to receive signals from the probe, wherein theprocessing system determines data corresponding to 1) variablesindicative of the optical parameters of a tissue being probed based onthe received signals and 2) variables related to a determinableparameter that accounts for the scattering and absorption of light bythe tissue, wherein the variables are mathematically formulated forcomparison to a previously obtained database of variables that a valuefor SpO₂ can be output that is indicative of SaO₂.